Monthly Archives: April 2011

A large Asian/Australasian study examined a 2hr triple-marker test in patients presenting with chest pain.

BACKGROUND: Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome.

METHODS: This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279.

FINDINGS: 3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11.8%) patients had a major adverse cardiac event. The ADP classified 352 (9.8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0.9%) of these patients, giving the ADP a sensitivity of 99.3% (95% CI 97.9-99.8), a negative predictive value of 99.1% (97.3-99.8), and a specificity of 11.0% (10.0-12.2).

INTERPRETATION: This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide.

In an accompanying editorial, nicely entitled ‘Acute MI: triple-markers resurrected or Bayesian dice?’ Dr Rick Body notes that the point-of-care triple-marker test has a relatively low sensitivity, at just 82.9%, when used alone, and the sensitivity only increased to 99.3% in the current study because it was used in an already-selected low-risk population. He writes: “Most people will probably consider this net risk to be statistically acceptable. However, if properly informed, low-risk patients might feel differently about the relative merits of waiting for definitive six-hour laboratory-based troponin testing or going home after two hours on the basis of results from a test that correctly identifies serious coronary disease, when present, in just over eight of 10 occasions.”

Dr Body has a new blog at The Bodsblog where we’re likely to be informed other data relevant to emergency cardiology as they emerge.

Point-of-care panel assessment using a similar triple-marker test at presentation and 90 minutes was also examined in the RATPAC study, in which it increased successful discharge home and reduced median length of stay, but did not alter overall hospital bed use.

Colorimetric CO2 detectors may fail to indicate successful tracheal tube placement in adults in certain circumstances, such as low cardiac output states, and waveform capnography is considered the gold standard. We now have data that demonstrate their inadequacy for neonatal intubation. Ideally, waveform devices should be used by all professionals who intubate patients – from paramedics to neonatologists.

AIM: Clinical assessment and end-tidal CO(2) (ETCO(2)) detectors are routinely used to verify endotracheal tube (ETT) placement. However, ETCO(2) detectors may mislead clinicians by failing to identify correct placement under a variety of conditions. A flow sensor measures gas flow in and out of an ETT. We reviewed video recordings of neonatal resuscitations to compare a colorimetric CO(2) detector (Pedi-Cap®) with flow sensor recordings for assessing ETT placement.METHODS: We reviewed recordings of infants <32 weeks gestation born between February 2007 and January 2010. Airway pressures and gas flow were recorded with a respiratory function monitor. Video recording were used (i) to identify infants who were intubated in the delivery room and (ii) to observe colour change of the ETCO(2) detector. Flow sensor recordings were used to confirm whether the tube was in the trachea or not.RESULTS: Of the 210 infants recorded, 44 infants were intubated in the delivery room. Data from 77 intubation attempts were analysed. In 35 intubations of 20 infants both a PediCap® and flow sensor were available for analysis. In 21 (60%) intubations, both methods correctly identified successful ETT placement and in 3 (9%) both indicated the ETT was not in the trachea. In the remaining 11 (31%) intubations the PediCap® failed to change colour despite the flow wave indicating correct ETT placement.CONCLUSION: Colorimetric CO(2) detectors may mislead clinicians intubating very preterm infants in the delivery room. They may fail to change colour in spite of correct tube placement in up to one third of the cases.

As far as I’m concerned the jury is still out here since this small study was terminated early, more patients in the montelukast group received magnesium and / or aminophylline, and it is unclear how the groups compared with regard to other other acute therapies such as beta-agonists and steroids.

BACKGROUND: Although leukotriene receptor antagonists have an established role in the management of patients with chronic asthma, their efficacy in an acute asthma exacerbation is not fully known.METHODS: 87 adults with acute asthma requiring hospitalisation were randomly assigned to receive either montelukast 10 mg or placebo on admission and every evening thereafter for 4 weeks (when they were reviewed as outpatients). All patients were admitted under the care of a consultant chest physician and received full care for acute asthma according to the British Thoracic Society guidelines. The primary end point was the difference in peak expiratory flow (PEF) between active and placebo treatment the morning following admission.RESULTS: Primary end point data were analysed for 73 patients. At study entry, patients who received montelukast (n=37) had a mean (±SD) PEF of 227.6 (±56.9) l/min (47.6% predicted) and those who received placebo (n=36) had a PEF of 240.3 (±99.8) l/min (49.6% predicted). The morning after admission, patients who received montelukast achieved a PEF of 389.6 (±109.7) l/min (81.4% predicted) compared with 332.3 (±124.9) l/min (69.8% predicted) for placebo (p=0.046). The mean difference between treatment groups was 57.4 l/min (95% CI of 1.15 to 113.6 l/min or 1.95-21.2% predicted).CONCLUSION: In acute asthma exacerbations the additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment.

I’m always on the look-out for evidence to guide vasoactive drug therapy, an area where much dogma is spouted by many who have not read the literature. Here’s a small (note: pilot) study comparing two strategies for cardiogenic shock. The higher heart rate and lactate with epinephrine (adrenaline) are consistent with the findings of the great CAT study; this is of interest, but not necessarily clinically significant nor practice changing.

OBJECTIVE: There is no study that has compared, in a randomized manner, which vasopressor is most suitable in optimizing both systemic and regional hemodynamics in cardiogenic shock patients. Hence, the present study was designed to compare epinephrine and norepinephrine-dobutamine in dopamine-resistant cardiogenic shock.DESIGN: Open, randomized interventional human study.SETTING: Medical intensive care unit in a university hospital.PATIENTS: Thirty patients with a cardiac index of <2.2 L/min/m and a mean arterial pressure of <60 mm Hg resistant to combined dopamine-dobutamine treatment and signs of shock. Patients were not included in cases of cardiogenic shock secondary to acute ischemic events such as myocardial infarction. Noninclusion criteria also included immediate indication of mechanical assistance.INTERVENTIONS: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain a mean arterial pressure of between 65 and 70 mm Hg with a stable or increased cardiac index.MAIN RESULTS: Both regimens increased cardiac index and oxygen-derived parameters in a similar manner. Patients in the norepinephrine-dobutamine group demonstrated heart rates lower (p<.05) than those in the epinephrine group. Epinephrine infusion was associated with new arrhythmias in three patients. When compared to baseline values, after 6 hrs, epinephrine infusion was associated with an increase in lactate level (p<.01), whereas this level decreased in the norepinephrine-dobutamine group. Tonometered PCO2 gap, a surrogate for splanchnic perfusion adequacy, increased in the epinephrine-treated group (p<.01) while decreasing in the norepinephrine group (p<.01). Diuresis increased in both groups but significantly more so in the norepinephrine-dobutamine group, whereas plasma creatinine decreased in both groups.CONCLUSIONS: When considering global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, epinephrine is associated with a transient lactic acidosis, higher heart rate and arrhythmia, and inadequate gastric mucosa perfusion. Thus, the combination norepinephrine-dobutamine appears to be a more reliable and safer strategy.

A patient develops shock and dyspnoea on the orthopaedic ward after a total knee replacement and massive pulmonary embolism is confirmed radiologically. Would you give a fibrinolytic or is it contraindicated? Harry Wright and colleagues did, but before giving 50 mg of intravenous rtPA they applied a tourniquet (Cryocuff) to the limb to limit the proportion of the systemic thrombolytic agent that would reach the site of the surgery. The tourniquet was inflated just before the infusion and was left on for one hour. There was some oozing of blood from the postoperative wound, which settled with bandage compression. The authors state that the inflation time of one hour was sufficient for the thrombolytic agent to be largely eliminated from the circulation, since alteplase has a plasma half-life of less than five minutes, although some plasminogen activator activity does persist for up to four hours.

The patient was well at three month follow up. They suggest:

Given the success in this case, we believe that major limb surgery no longer represents a contraindication to thrombolysis.

There is now a single use flexible intubating device that compares favourably with conventional fibreoptic devices. It does not have fibreoptic cables, but rather has a small camera at its tip illuminated by an LED. The image is transmitted via a cable in the device to a reusable screen. Dr Cook’s team in Bath, England have an extensive track record of evaluating new airway devices, and they report their assessment of this gadget in a manikin-based study. I think this may extend the airway management options to departments or teams for whom the cost and maintenance of conventional fibreoptic equipment is prohibitive.

We compared the Ambu aScope™ with a conventional fibrescope in two simulated settings. First, 22 volunteers performed paired oral and nasal fibreoptic intubations in three different manikins: the Laerdal Airway Trainer, Bill 1 and the Airsim (a total of 264 intubations). Second, 21 volunteers intubated the Airway Trainer manikin via three supraglottic airways: classic and intubating laryngeal mask airways and i-gel (a total of 66 intubations). Performance of the aScope was good with few failures and infrequent problems. In the first study, choice of fibrescope had an impact on the number of user-reported problems (p=0.004), and user-assessed ratings of ease of endoscopy (p<0.001) and overall usefulness (p<0.001), but not on time to intubate (p=0.19), or ease of railroading (p=0.72). The manikin chosen and route of endoscopy had more consistent effects on performance: best performance was via the nasal route in the Airway Trainer manikin. In the second study, the choice of fibrescope did not significantly affect any performance outcome (p=0.3), but there was a significant difference in the speed of intubation between the devices (p=0.02) with the i-gel the fastest intubation conduit (mean (SD) intubation time i-gel 18.5(6.8)s, intubating laryngeal mask airway = 24.1(11.2)s, classic laryngeal mask airway = 31.4(32.5)s, p=0.02). We conclude that the aScope performs well in simulated fibreoptic intubation and (if adapted for untimed use) would be a useful training tool for both simulated fibreoptic intubation and conduit-assisted intubation. The choice of manikin and conduit are also important in the success of such training. This manikin study does not predict performance in humans and a clinical study is required.

Awake fibreopic intubation (AFOI) is indicated in a subgroup of critically ill patients in whom RSI is contraindicated due to a predicted difficult airway, and in whom time pressures do not mandate a more immediate route to the airway. Last night I intubated a patient with a swollen tongue using this technique, under remifentanil sedation. It was interesting to subsequently see that this month’s Anaesthesia contains an article on ‘remi’ for AFOI:

Remifentanil is increasingly being used as the primary agent to provide sedation during awake fibreoptic nasal intubation. In this observational study, we aimed to determine the optimal effect site concentration of remifentanil, using a target controlled infusion based on the Minto pharmacological model, to provide optimal safe intubation conditions without the use of other sedatives/premedication and/or spray-as-you-go local anaesthesia. Twenty patients with anticipated difficult airway participated in the study. Good intubating conditions were achieved in all patients with mean (SD) effect site concentration of 6.3 (3.87) ng.ml(-1) of remifentanil recorded at nasal endoscopy and 8.06 (3.52) ng.ml(-1) during tracheal intubation. No serious adverse event occurred during any of these procedures. These preliminary findings suggest that this is a feasible and safe technique for awake fibreoptic nasal intubation.

Those of us not familiar with target controlled infusions might find a dose in micrograms per kilo more helpful. This paper from Analgesia and Anesthesia provides a useful guide, comparing relatively high and low doses of loading and maintenance doses:

Awake nasotracheal fiberoptic intubation requires an anesthetic management that provides sufficient patient comfort, adequate intubating conditions, and stable hemodynamics. Short-acting and easily titratable analgesics are excellent choices for this maneuver. In this study, our aim was to determine an appropriate dosage regimen of remifentanil for awake nasotracheal fiberoptic intubation. For that reason, we compared two different dosage regimens. Twenty-four patients were randomly assigned to receive remifentanil 0.75 micro g/kg in bolus, followed by a continuous infusion of 0.075 micro g x kg(-1) x min(-1) (Group L), or remifentanil 1.5 micro g/kg in bolus, followed by a continuous infusion of 0.15 micro g x kg(-1) x min(-1) (Group H). All patients were premedicated with midazolam 0.05 mg/kg IV and glycopyrrolate 0.2 mg IV. Both dosage regimens ensured patient comfort and sedation. Discomfort did not differ between groups. Patients in Group H were sedated more profoundly. Hemodynamic stability was maintained with both remifentanil doses. Intubating conditions were adequate in all patients and comparable between the groups. The large dosage regimen did not result in any additional benefit compared with the small dosage. For awake nasotracheal fiberoptic intubation, we therefore recommend remifentanil 0.75 micro g/kg in bolus followed by continuous infusion of 0.075 micro g x kg(-1) x min(-1), supplemented with midazolam 0.05 mg/kg

An alternative to bolus + maintenance is using an incremental infusion rate via an infusion pump. In a comparision with midazolam and fentanyl, remifentanil was given to 37 patients in incremental dosages (0.1-0.25-0.5 microg/kg/min) by an infusion pump according to comfort, level of sedation and respiratory depression. Nasotracheal intubation was better tolerated in the remifentanil group, who also showed better suppression of haemodynamic effects of intubation.

BACKGROUND: Awake fiberoptic intubation is the standard of care for difficult airway management. Quality and success of this technique depend on the experience of the intubating physician and the proper preparation of the patient. The aim of this study was to compare remifentanil (R) as single agent to the combination of fentanyl (F) and midazolam (M), which have been the drugs for analgesia and sedation for this procedure.

METHODS: Seventy-four adult patients requiring nasotracheal intubation were randomly assigned to one of two groups. In group I, (n=37) R was administered in incremental dosages (0.1-0.25-0.5 microg/kg/min) by an infusion pump according to comfort, level of sedation and respiratory depression. In group II, (n=37) analgesia and sedation was achieved by F 1.5 microg/kg and doses of between 1 and 10 mg M, titrated to the individual needs. Patient reactions like grimacing, movement and coughing during intubation were assessed, as well as patient recall of the procedure. Haemodynamic and respiratory parameters were continuously recorded.

RESULTS: Group I patients better tolerated nasal tube passage (P<0.001) and laryngeal tube advancement (P<0.001) than group II. Remifentanil better suppressed hemodynamic response to nasal intubation (P<0.001). No significant difference in respiratory data was recorded. In group I more recall of the procedure was observed (six vs. zero patients, P<0.05).

CONCLUSION: Remifentanil in high doses, as the single agent for patient preparation for awake fiberoptic intubation seems to improve intubating conditions, quality and reliability of the procedure. However, a higher incidence of recall is to be expected.

Some authors advocate dexmedetomidine for AFOI. Remifentanil was compared with dexmedetomidine in a randomised, double-blind trial. Remi was loaded and maintained at the ‘low’ dose as described in the second paper above and was associated with a higher intubation success rate on first attempt than dexmedetomidine (76% vs 38%):

Introduction: Dexmedetomidine (DEX), a centrally acting, selective alpha-2 agonist, with analgesic and sedation properties, has been successfully used for sedation in intensive care units. Remifentanil (REM), an ultra-short acting synthetic opioid, is often used to aid awake fiberoptic intubation (AFOI). As a narcotic, REM has a potential for respiratory depression, whereas DEX does not. This study compares the use of REM and DEX as adjuncts to local anesthetic preparation of the airway for AFOI.

Methods: Thirty adult ASA I-III patients with expected difficult airways were randomized to receive REM or DEX for sedation during AFOI. Operators and assessors were blinded to the drug used. Preoperatively, all patients received 2 mg midazolam intravenously and their airways were topicalized with 4% lidocaine. Patients in the REM group received a bolus of 0.75 mcg/kg over 10 minutes followed by an infusion of 0.075 mcg/kg/min. Patients in the DEX group received a bolus of 0.4 mcg/kg over 10 minutes followed by an infusion of 0.7 mcg/kg/hr. A word and picture set was presented to each patient before any drugs were administered, after loading of either sedative, and following extubation. Heart rate, blood pressure, respiratory rate, SpO2, bispectral (BIS) index level, and Ramsay sedation level (RSS) were recorded. Recall of each 3 sets of pictures and words was assessed at 30 minute intervals for a period of 3 hours after the completion of surgery.

Results: Patient demographics were similar between the 2 groups. All patients’ airways were successfully secured by fiberoptic intubation. Seventy-six percent of REM cases were intubated on the first attempt, as compared to 38% of the DEX cases (p=0.02). Intubation attempts were greater in the DEX group even after adjusting for confounders (OR unadjusted = 5.26, 95% C.I. = 1.19, 25.72; OR adjusted = 4.84, 3.43, 6.82). The DEX group had a higher mean oxygen saturation rate than REM (1.58 higher; 95% C.I. = 0.14, 3.03; p=0.03). Although the incidence of O2 saturation < 90% was greater in the REM group, it was not significant. No apneic episodes occurred and no rescue maneuvers, such as administration of reversal drugs or positive pressure ventilation, were required in either group. There was a lower Ramsey Sedation Scale (RSS) score (lower by = 0.45, 95% C.I. = 0.1142, 0.7792; p=0.008) in the DEX group compared to the REM group. A Kaplan Meier survival analysis showed that DEX patients took longer to attain a RSS of 3 despite reaching a lower RSS score. (Logrank test = 4.00 with one degree of freedom, p=0.0455) The DEX group also had 6.99 lower (95% C.I. = 1.19, 12.79; p=0.018) BIS score compared to the REM group. Generalized estimating equations (xtgee) showed no significance in the recall results with the exception of verbal recall in the DEX group after the initial bolus. Minimal hemodynamic instability was observed in both groups.

Discussion: Both Dex and REM can be safely used as sedative agents for AFOI. Despite increased sedation and lower recall after the initial bolus, the DEX group required more attempts at intubation. Nonetheless, lower oxygen saturation was observed in the REM group.

The eighth Report of the Confidential Enquiries into Maternal Deaths in the UK investigates the deaths of 261 women who died in the triennium 2006–08, from causes directly or indirectly related to pregnancy.

Direct deaths (from medical conditions that can only be the result of pregnancy) significantly decreased from 6.24 per 100 000 maternities in the last triennium to 4.67 per 100 000 maternities in this triennium (P = 0.02). This equates to 25 fewer direct maternal deaths over the triennium, and this decline is predominantly the result of reductions in deaths from thromboembolism, and to a lesser extent, haemorrhage. The case fatality rate for ectopic pregnancy has almost halved from an estimated rate of 31.2 per 100 000 estimated ectopic pregnancies in 2003–05 to 16.9 in this triennium.

Although Direct maternal deaths have decreased overall there has been a dramatic increase in deaths related to genital tract sepsis, particularly from community-acquired Group A streptococcal disease. The overall rate has increased from 0.85 deaths per 100 000 maternities in 2003–05 to 1.13 deaths in this triennium. Sepsis is now the commonest cause of Direct maternal deaths in the UK and this has prompted a Clinical Briefing from the Centre for Maternal and Child Enquiries (CMACE) alerting health professionals to the risks.

Indirect maternal death rates have remained largely unchanged since the last report. Cardiac disease remains the most common cause of Indirect maternal death: many of these women also had lifestyle-related risk factors for cardiac disease: obesity, smoking and increased maternal age.

The review revealed many of the deaths to be associated with substandard care, some of the challenges being:

ABSTRACT In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006–2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United KingdomBJOG. 2011 Mar;118 Suppl 1:1-203 (Full text available from CMACE site)

Outcomes are described for military personnel with vascular injury sustained in Afghanistan and Iraq.

BACKGROUND: Military injuries to named blood vessels are complex limb- and life-threatening wounds that pose significant difficulties in prehospital and surgical management. The aim of this study was to provide a comprehensive description of the epidemiology, treatment and outcome of vascular injury among service personnel deployed on operations in Afghanistan and Iraq.

METHODS: Data from the British Joint Theatre Trauma Registry were combined with hospital records to review all cases of vascular trauma in deployed service personnel over a 5-year interval ending in January 2008.

RESULTS: Of 1203 injured service personnel, 110 sustained injuries to named vessels; 66 of them died before any surgical intervention. All 25 patients who sustained an injury to a named vessel in the abdomen or thorax died; 24 did not survive to undergo surgery and one casualty in extremis underwent a thoracotomy, but died. Six of 17 patients with cervical vascular injuries survived to surgical intervention; two died after surgery. Of 76 patients with extremity vascular injuries, 37 survived to surgery with one postoperative death. Interventions on 38 limbs included 19 damage control procedures (15 primary amputations, 4 vessel ligations) and 19 definitive limb revascularization procedures (11 interposition vein grafts, 8 direct repairs), four of which failed necessitating three amputations.

CONCLUSION: In operable patients with extremity injury, amputation or ligation is often required for damage control and preservation of life. Favourable limb salvage rates are achievable in casualties able to withstand revascularization. Despite marked progress in contemporary battlefield trauma care, torso vascular injury is usually not amenable to surgical intervention.